The effects of tetrodotoxin‐induced muscle paralysis on the physiological properties of muscle units and their innervating motoneurons in rat.

Abstract

Physical Activity Sciences Programme, Departement d'education physique, Universitet de Montre'al, CP 6128, succursale 'Centre-ville', Montre'al, Quebec H3C 3J7, Canada 1. Although the inactivity of a slow muscle (cat soleus) induced via nerve impulse blockade has been demonstrated to have some axotomy-like effects (decreased after-hyperpolarization (AHP) duration) on its innervating motoneurons, the reported effects of inactivity on motoneurons which innervate fast muscles containing mixtures of motor unit types are equivocal. This study was designed to determine the effect of a period (2 weeks) of complete hindlimb muscle paralysis, via tetrodotoxin (TTX) blockade of sciatic nerve impulses, on the contractile (muscle units) and electrophysiological (motoneurons) properties of motor units in the rat gastrocnemius. Motoneuron properties were also compared with those of rats subjected to sciatic nerve axotomy 2 weeks earlier. 2. At the time of the terminal experiment (24 h after the removal of the TTX delivery system) in anaesthetized animals, properties of tibial motoneurons (i.e. rheobase current, input resistance, time course of after-potentials) were determined using conventional microelectrode techniques. For those tibial motoneurons innervating the gastrocnemius, muscle unit responses (i.e. twitch force and time course, maximum tetanic tension, fatigability) were also recorded in response to current injection. 3. Consistent with previously reported whole-muscle responses to TTX-induced disuse, the TTX-treated gastrocnemius muscle units showed weaker tetanic forces, prolonged twitches and elevated twitch/tetanic ratios. These effects were similar for motor units classified as small, medium and large according to their tetanic tension-generating capacities. Muscle unit fatigue resistances appeared to be unchanged. 4. The mean values, distributions and ranges of tibial motoneuron properties were similar between control and TTX-treated groups for rheobase, input resistance and AHP half-decay time. In the case of the latter, the proportion of motoneurons possessing 'slow' AHP halfdecay times (> 20 ms) was not significantly different in control (17%) and TTX-treated groups (11 %). 5. Motoneurons axotomized 2 weeks earlier had a significantly higher (42-69%) mean input resistance and a longer (34-42%) mean AHP half-decay time when compared with the control and TTX-treated groups.6. It appears that, for fast muscles containing several different motor unit types, TTX-induced axon blockade does not produce similar effects on motoneuron intrinsic properties to those evoked by axotomy. This lack of effect on the distribution and range of these properties of tibial motoneurons indicates that none of the motoneurons which innervate muscles of mixed fibre type are particulary susceptible to the decreased activity and the atrophyassociated muscle changes produced by this condition. Thus, the apparent 'retrograde signalling' of muscle on motoneuron properties reported previously for the cat soleus may be specific to this par...

Enhanced Transmission at a Spinal Synapse TriggeredIn Vivoby an Injury Signal Independent of Altered Synaptic Activity

“…For AHP half-decay time, none of the treatment groups exhibited a significant difference from normal. This finding is consistent with previous demonstrations that changes in AHP occur more slowly after various nerve treatments in rat, including crush (Gardiner and Seburn, 1997). It also suggests that comparison of group means for IA EPSP amplitude was not confounded by bias in the MNs sampled in each group.…”

Regulation of Motoneuron Excitability via Motor Endplate Acetylcholine Receptor Activation

“…The mean rheobase current for all of the experiments after axotomy was 4.5 Ϯ 0.34 nA, which was significantly lower than the mean rheobase current of control animals (11.5 Ϯ 0.61 nA; p Ͻ 0.001). The decrease in rheobase current is similar to the effects of axotomy on motoneuron electrical properties reported previously in rats (Gardiner and Seburn, 1997) and in cats (Foehring et al, 1986b;Pinter and Vanden Noven, 1989). Neither AHP halfdecay nor MG motor axon conduction velocity showed significant changes 5 d after axotomy relative to control motoneurons ( p Ͼ 0.05).…”

“…Neither AHP halfdecay nor MG motor axon conduction velocity showed significant changes 5 d after axotomy relative to control motoneurons ( p Ͼ 0.05). Because changes in these properties are observed at longer postaxotomy intervals (Gardiner and Seburn, 1997), this indicates that these motoneuron properties change after axotomy with a longer time course than rheobase current. Differences in the rate at which electrical properties change after axotomy have also been observed in cat motoneurons, with rheobase current exhibiting the fastest change (single-exponential time constant, 2.3 d) (M. J. Pinter, unpublished observations).…”

“…The possibility that such activity may have occurred prevents distinguishing confidently whether small amounts of ACh release or small amounts of muscle fiber activity inhibited rheobase changes after botox. Other studies have shown, however, that the blockade of motor axon action potentials in cats (Webb and Cope, 1992) and in rats (Gardiner and Seburn, 1997) for as long as 2 weeks does not produce axotomy-like changes in gastrocnemius motoneuron rheobase current. Complete loss of muscle activity is thus not sufficient to evoke axotomy-like changes in gastrocnemius motoneurons, and other factors must continue to maintain normal motoneuron properties.…”

“…These findings support the idea that at least some motoneuron properties might be regulated by muscle activity. It may, however, be significant that Czeh et al (1978) studied motoneurons innervating the cat soleus muscle (which contains purely slow motor units), whereas the other studies in which TTX paralysis produced no changes studied motoneurons innervating the mixed-type gastrocnemius muscle in cat and rat, which feature a large proportion of fast motor units (Webb and Cope, 1992;Gardiner and Seburn, 1997). Previous studies have shown that motoneurons innervating slow-type units fire many more action potentials on a daily basis than do motoneurons that innervate fast-type motor units (Henning and Lomo, 1985).…”